Jin B, Scott J L, Vadas M A, Burns G F
Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, South Australia.
Immunology. 1989 Apr;66(4):570-6.
This study analysed the regulatory effects of transforming growth factor beta (TGF beta) on the expression of a 70,000 MW cell surface activation antigen, TLiSA1, involved in the differentiation of cytotoxic T lymphocytes (CTL) and lymphokine-activated killer (LAK) cells from their precursor(s), and also examined the role of TGF beta in the generation of these functional cells. TGF beta was shown to suppress the expression of TLiSA1 and to inhibit, in a dose-dependent manner, the generation of both CTL and LAK cells when present from the beginning of mixed lymphocyte culture; the same inhibitory effect upon the development of cytotoxic effector cells was observed with a monoclonal antibody and with monospecific rabbit antibodies against the TLiSA1 protein. Antibody to TGF beta reversed the inhibitory effect of the cytokine on differentiation and on TLiSA1 expression. Exogenous IL-2 or, to a lesser extent, tumour necrosis factor alpha (TNF alpha) added to mixed lymphocyte cultures (MLC) augmented both TLiSA1 antigen expression and cytotoxic function by the resulting blast cells; the co-addition of TGF beta inhibited both of these cytokine-mediated effects. Similarly, it was shown that phytohaemagglutini (PHA)-induced lymphoblasts up-regulate their surface expression of TLiSA1 and exhibit increased LAK activity in response to IL-2, and TGF beta inhibited both of these events; this IL-2-induced increase in LAK cell function was also inhibited by antibodies to TLiSA1. It is suggested that TLiSA1 antigen expression is intimately linked to the differentiation of cytotoxic effector cells and that such differentiation may be a distinct process from IL-2-induced proliferation, although both events can be regulated by TGF-beta.
本研究分析了转化生长因子β（TGFβ）对一种分子量为70,000的细胞表面活化抗原TLiSA1表达的调节作用，该抗原参与细胞毒性T淋巴细胞（CTL）和淋巴因子激活的杀伤细胞（LAK）从其前体细胞的分化过程，同时还研究了TGFβ在这些功能细胞生成中的作用。结果显示，TGFβ可抑制TLiSA1的表达，并在混合淋巴细胞培养开始时就以剂量依赖的方式抑制CTL和LAK细胞的生成；用抗TLiSA1蛋白的单克隆抗体和单特异性兔抗体对细胞毒性效应细胞的发育也观察到了同样的抑制作用。抗TGFβ抗体可逆转该细胞因子对分化和TLiSA1表达的抑制作用。向混合淋巴细胞培养物（MLC）中添加外源性白细胞介素-2（IL-2）或在较小程度上添加肿瘤坏死因子α（TNFα），可增强由此产生的母细胞的TLiSA1抗原表达和细胞毒性功能；同时添加TGFβ可抑制这两种细胞因子介导的效应。同样，研究表明，植物血凝素（PHA）诱导的淋巴细胞可上调其TLiSA1的表面表达，并在对IL-2的反应中表现出增强的LAK活性，而TGFβ可抑制这两个过程；抗TLiSA1抗体也可抑制IL-2诱导的LAK细胞功能增强。提示TLiSA1抗原表达与细胞毒性效应细胞的分化密切相关，并且这种分化可能是一个与IL-2诱导的增殖不同的过程，尽管这两个过程均可受TGF-β的调节。
